INHIBITION OF MIXED LEUKOCYTE-CULTURE REACTION BY 8-METHOXYPSORALEN AND LONG-WAVELENGTH ULTRAVIOLET-RADIATION

[摘要] Psoriasis patients receiving therapy with oral 8-methoxypsoralen plus long-wavelength UV radiation have diminished leukocyte DNA synthesis and immune reactivity. To quantitate the immunological effects of therapeutic concentrations of 8-methoxypsoralen plus long-wavelength UV radiation, the mixed leukocyte culture reaction was measured in vitro. Leukocytes treated with 8-methoxypsoralen were exposed to plate glass filtered UV radiation from a bank of PUVA fluorescent lamps. To evaluate the (2-way) mixed leukocyte reaction, treated leukocytes were mixed with untreated leukocytes from another donor in microtiter wells, and tritiated thymidine incorporation was measured after 4-6 days. To measure stimulation or proliferation ability (1-way mixed leukocyte reactions), treated or untreated leukocytes were exposed to 2000 R X-radiation prior to mixing. Treatment of leukocytes with 8-methoxypsoralen (0.01, 0.1 or 1.0 .mu.g/ml) followed by 7000-87,000 J/m2 long-wavelength UV radiation resulted in a dose-dependent inhibition of mixed leukocyte culture reactivity. 0.1 .mu.g/ml 8-methoxypsoralen plus 7000 J/m2 UV radiation resulted in a 48% reduction in mixed leukocyte reaction-induced tritiated thymidine incorporation in the 2-way assay. 1 .mu.g/ml 8-methoxypsoralen plus 87,000 J/m2 UV radiation virtually abolished reactivity in the 2-way mixed leukocyte reaction, and in both 1-way mixed leukocyte reactions. Exposure to 87,000 J/m2 long wavelength UV radiation alone resulted in 45% inhibition of stimulation ability. Therapeutic concentrations of 8-methoxypsoralen followed by exposure to long-wavelength UV radiation inhibited both the stimulating ability and the mixed leukocyte culture reaction-induced proliferation of peripheral blood leukocytes in vitro.